Structure of the DBD

p73 is a protein comprised of 636 amino acids. Its full structure has yet to be discovered, and this is an area we think should be explored.

The first structures of the p73 DNA binding domain (DBD) have been determined by X-ray crystallography. The DBD makes up 198 residues of p73 and it is the most conserved region of the protein.

Its main structural features are:

• a core immunoglobulin-like β-sandwich fold, of which one sheet contains 4 β-strands (S1, S3, S5, S8) and the other 5 β-strands (S4, S6, S7, S9, S10)
• 3 long loops emerging from the β-sandwich (L1, L2, L3); L1 contains 2 small β-strands called S2 and S2’; L2 is divided into L2A and L2B
• 3 α-helices (H1, H2 and 3(10)H)

Figure 2  shows A) a monomer of the DBD containing these features and B) the amino acids which contribute to them

Figure 2: A) Structure and fold of the p73 DBD monomer, showing 3 α-helices (cyan), 10 β-sheets (magenta) and  3 loops (pink), as well as chelated Zn²⁺ (yellow). B) ClustalW multiple sequence alignment of human p73α and p73β showing residues contributing to α-helices, β-sheets and loops (colour-coded to match A))

2 Zn²⁺ ions are chelated by the DNA binding domain, and are crucial for dimerization and DNA binding (see Figure 1A).

Techniques

• X-ray crystallography was used to determine the structure to the p73 DNA binding domain